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GI/GU Exam > Liver Biochemistry > Flashcards

Liver Biochemistry Flashcards

1
Q

What is the structure of the liver?

A

4 lobes: right, left, caudate, quadrate

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2
Q

What is the blood supply to the liver?

A 
The hepatic portal vein - brings nutrient-rich venous blood from GI tract (75%)
hepatic arteries (25%)
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3
Q

What are the cells of the liver? (6)

A 
hepatocytes
endothelial cells
hepatic stellate cells
cholangiocytes
pit cells
kupffer cells
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4
Q

What is the function of hepatocytes?

A

They’re the main cell type in the liver (80%), carry out metabolic liver functions.

CAN REGENERATE

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5
Q

What is the function of liver endothelial cells?

A

Allow exchange b/w liver and blood via pores & fenestrations in their plasma membrane

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6
Q

What is the function of hepatic stellate cells?

A

Are storage site for Vitamin A and other lipids

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7
Q

What is the function of cholangiocytes?

A

They line the bile duct, control bile flow rate and bile pH

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8
Q

What is the function of pit cells?

A

These are NK cells that protect liver from viruses and tumors (lymphocytes)

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9
Q

What is the function of Kupffer cells? (4)

A
  • Protect liver from gut-derived microbes
  • Remove dead cells
  • orchestrate immune response
  • secrete cytokines
    Line the sinusoids. Are specialized macrophages w/good endocytic & phagocytic function and lots of lysosomes
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10
Q

What are the general functions of the liver? (8

A
  • Carbohydrate metabolism
  • Lipid metabolism
  • Nucleotide biosynthesis
  • Protein and amino acid metabolism
  • Removal of nitrogen generated by protein & aa metabolism
  • Bilirubin metabolism
  • Synthesis of blood proteins
  • Deactivates/detoxes/biotransforms metabolites and xenobiotics
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11
Q

What specifically does the liver do in carbohydrate metabolism? (6)

A 
Glucostasis (keep blood gluc stable)
Glycogen synthesis
Glycogenolysis
Gluconeogenesis
Makes ketones when starving
Has Glucose-6-phosphatase to release free gluc to blood
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12
Q

What does the liver do in lipid metabolism? (3)

A

Biosynthesizes fats
Degrades fats
Regulates FFA Metabolism (making and breaking)

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13
Q

What proteins does the liver synthesize? (7)

A 
Acute phase proteins
 - CRP
 - protease inhibitors
 - alpha-1 antitrypsin
 - alpha-1 antichymotrypsin
albumin
IgG
apoproteins
fibrinogen
prothrombin
clotting factors V, VII, IX, X
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14
Q

What ways has the liver adapted to facilitate its function? (3)

A

circulation
structural
cellular

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15
Q

What circulatory adaptations does the liver have to facilitate its function?

A

It gets blood from enteric circulation and the periphery so it can have first pass for ingested substances

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16
Q

What structural adaptations does the liver have to facilitate its function?

A
  • No basement membrane
  • No tight junctions b/w hepatocytes and endothelial cells
  • gaps b/w endothelial cells
  • pores in endothelial membrane
    Basically all this to allow more contact between the liver and blood
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17
Q

What cellular adaptations does the liver have to facilitate its function?

A

Well-developed plasma membrane and ER, lots of lysosomes and metabolic enzymes

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18
Q

What are the steps of emulsification? (4)

A
  1. cholic acid (bile acid) ionizes to give bile salt
  2. hydrophobic surface of bile salt associates w/TAG, several complexes aggregate to form micelle
  3. hydrophobic surface of bile salt faces out, allows micelle to interact w/ pancreatic lipase
  4. hydrophobic action of lipase frees FA’s to break into smaller micelle that’s absorbed through intestinal mucosa
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19
Q

What are the primary bile acids?

A
  • chenodeoxycholic acid

- cholic acid

20
Q

What are the secondary bile acids?

A
  • deoxycholic acid

- lithocholic acid

21
Q

What is the difference between primary and secondary bile acids?

A

Primary - synthesized in liver

Secondary - result from bacterial action in colon. Also have no -OH on carbon 7. They inhibit 7 alpha-hydroxylase!

22
Q

What are gallstones?

A

Supersaturated gallbladder bile with cholesterol crystals

23
Q

What can cause gallstones? (3)

A
  • inefficient bile salt secretion
  • inefficient phospholipid secretion
  • excess cholesterol secretion
24
Q

What is the treatment for gallstones? (2)

A

If too big, cholecystectomy
If small enough, can treat with oral ursodeoxycholic acid, a secondary bile acid that reduces cholesterol secretion, increases biliary cholesterol solubility

25
Q

How do cholesterol-lowering drugs work? (4 steps)

A
  1. bind to bile, causing more of it to be excreted
  2. bile acid synthesis rate increases by induction of 7alpha-hydroxylase
  3. liver cholesterol pool depleted, increased uptake of LDL into liver
  4. lowered plasma cholesterol levels!
26
Q

What is one cholesterol-lowering drug?

A

cholestyramine

27
Q

What are metabolites?

A

By products of metabolism that your body makes

28
Q

What are xenobiotics?

A

medicines/substances taken from ‘outside’

29
Q

What are the steps of phase 1 reactions of detoxification of xenobiotics?

A
  • Reduction
  • Oxidation
  • Hydroxylation
  • Hydrolysis
30
Q

What is the purpose of the phase one reaction?

A

To make a more polar primary metabolite

31
Q

What catalyzes the phase 1 reaction?

A

P450 Enzyme (CYP)

32
Q

What are the steps of the phase 2 reaction?

A
  • Conjugation
  • Sulfation
  • Methylation
  • Glucuronidation
33
Q

What is the purpose of the phase 2 reaction?

A

The functional groups are conjugated for safe excretion

34
Q

What are cytochrome P450 enzymes?

A

A superfamily of enzymes that play a key role in the metabolism of multiple hydrophobic compounds

35
Q

What enzyme do CYP enzymes co-localize with?

A

cytochrome p450 reductase (CYPR)

36
Q

Why is CYPR important?

A

It is the rate-limiting enzyme

37
Q

Which 3 CYP enzymes are the most important?

A

CYP1, CYP2, CYP3

38
Q

What are other electron transport systems? (correlation box)

A

Are in the ER, act as mono-oxidases by utilizing pairs of e- from NADPH to incorporate molecular oxygen into the substrate while reducing a second O2 to water

39
Q

How do Cytochrome P450 and drugs interact? (correlation box)

A

Certain drugs increase the rate of reactions, some form a complex with CYP that inhibit them:
drugs that inhibit CYP = increase drug levels of plasma
drugs that stimulate CYP = decrease drug levels in plasma

40
Q

What is an example of a substance that inhibits CYP?

A

Citrus juices (esp grapefruit juice)

41
Q

What is an example of a substance that stimulates CYP?

A

St. John’s Wort

42
Q

What sort of changes to the liver do you see in cases of liver disease?

A
  • Normally-leaky basement membrane replaced by dense membrane w/lots of fibrillar collagen
  • fenestrations in plasma membrane & space b/w endothelial junctions lost
  • Hepatic vascular channels get stiffer, increasing resistance and intra-sinusoidal fluid pressure (portal HTN)

Basically all the normal junk is donked (free exchange of material impaired)

43
Q

What are liver function tests? (9)

A
  • Albumin
  • Transaminases (ALT/AST)
  • Alkaline phosphatase
  • prothrombin time
  • bilirubin (conj/unconj)
  • urea
  • glucose
  • TAG
  • cholesterol
44
Q

Which tests are the best indicators of liver damage?

A

ALT/AST (ALT more sensitive), they increase in liver disease

45
Q

Where are ALT/AST found?

A

Both found in mitochondria, but ALT also found in cytosol

46
Q

What are the steps of bile acid synthesis?

A
  1. conversion of cholesterol to 7 alpha-hydroxycholesterol by 7 alpha-hydroxylase (committed step)
  2. reduction, hydroxylation, conversion of hydroxyls to alpha becomes 3 alpha, 7alpha-diol
  3. diverge now - an oxidation of a side chain leads to 3 alpha, 7 alpha, 12, alpha-triol to CHOLIC ACID or conversion of 3 alpha, 7 alpha-diol to CHENODEOXYCHOLIC ACID
  4. cholic acid converted to cholyl coA, which is converted to taurocholic acid
  5. cholyl coA becomes glycocholic acid
47
Q

Which bile acid is most effective?

A

Taurocholic acid, because the pKa is lower meaning it is more ionizing (better detergent)

GI/GU Exam (21 decks)

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